Author Of 2 Presentations
P0332 - Evaluating the Efficacy and Safety of Transitioning Patients from Natalizumab to Ocrelizumab (OCTAVE) (ID 439)
Abstract
Background
Natalizumab (NTZ) is an effective therapy for patients with relapsing MS (RMS). However, it is associated with a risk of progressive multifocal leukoencephalopathy (PML) in patients infected with John Cunningham virus (JCV). Ocrelizumab (OCR) has demonstrated efficacy, yet its safety in patients previously treated with NTZ is unclear.
Objectives
To present interim data from OCTAVE, a prospective, observational study to evaluate the efficacy and safety of OCR in RMS patients previously treated with NTZ.
Methods
Clinically and radiologically stable RMS patients, aged 18-65 treated with a stable dose of NTZ for ≥ 12 months, were started on OCR 4-6 weeks after last dose of NTZ and followed for 12 months. Relapse assessment, Expanded Disability Status Scale (EDSS), and MRI were performed prior to starting OCR and at months 3, 6, 9 (no MRI), and 12.
Results
Thirty-seven patients, 75.7% female with mean age of 43.8 (± 10.97) and a median of 33.5 [IQR = 63.2] NTZ infusions prior to starting OCR have been enrolled between August 9th, 2017 and February 3rd, 2020. 23 patients have completed the study duration of 12 months. Thirty-one subjects switched to OCR due to potential PML risk. One patient had a clinical relapse reported at month 12 although no MRI correlate. However, EDSS at baseline was 4.0 and at month 12 the score was 5.5. At month 3, one patient had one enhancing lesion, and one patient had 3 enhancing lesions. At months 6 and 12, there were no enhancing or new/enlarging T2 lesions. There were no significant changes in the EDSS, physical MSIS-29, and psychological MSIS-29 from baseline to months 6 and 12, though there was an increasing trend for EDSS. Median EDSS [IQR] was 3.00 [2.0] at baseline and median EDSS [IQR] was 4.00 [2.50] at month 12. Infusion reactions were seen in 40.5% of patients with the first dose (includes both 300mg infusions) and 13.5 % with the second dose (600mg infusion). Eight serious adverse events (SAEs) have been reported with three possibly related to OCR, breast cancer, urinary tract infection, and acute cystitis. No cases of PML have been reported.
Conclusions
The transition from NTZ to OCR resulted in limited disease activity. In 2 patients, MRI activity was present at 3 months, but no MRI changes were seen at months 6 and 12. One patient was reported to have a clinical relapse at month 12; however, there were no MRI changes. The trend in increasing EDSS is concerning.
P0407 - The Impact of Ocrelizumab on Immunoglobulin Levels and the Risk of Infection. (ID 476)
Abstract
Background
Ocrelizumab (OCR), an anti-CD20 antibody, was approved in the US in March 2017 for treating relapsing (RMS) and primary progressive MS (PPMS). Infections were more commonly seen in patients receiving OCR in earlier trials. Last year European Medicines Agency updated the OCR prescribing information to include the association between a reduction in immunoglobulins especially IgG and serious infections.
Objectives
To determine if there is a relationship in baseline and follow up immunoglobulins levels and the risk of having an infection
Methods
MS patients in our OCR registry with at least one IgM/IgG value and who received ≥2 doses of OCR were included. IgG/IgM levels were obtained within a month of each infusion. Wilcoxon rank-sum tests and linear models were used to examine the relationships between IgM/IgG and infections.
Results
337 patients were included. 72.4% were female; median age was 53.2 [IQR = 19.8] years with a median disease duration of 13.5 [IQR = 11.8] years. 78% had RMS, 13.4% had SPMS, and 8.6% had PPMS. 27% of patients were treatment naïve. Median time on OCR was 26 [IQR = 8.9] months. 88.7% of patients had more than one IgG and IgM value. Infections were seen in 226 (67.1%) patients. The median age of patients who did and did not have an infection was 53.5 [IQR =20.2] and 53 [IQR = 18.1] respectively. Prior natalizumab use was associated with a higher rate of infection, 46 of 62 (74%). No significant differences were found between IgM levels nor IgG levels for cases of infection (56 [IQR = 53], 792 [IQR = 294.5] mg/dL) and non-infection (52 [IQR = 51], 828.5 [IQR = 310.2]) mg/dL) (
Conclusions
Older patients with longer duration of disease and OCR therapy have been found to have more infections, but we did not observe age as a risk factor for infection in this cohort. Furthermore, neither baseline nor follow up IgM or IgG levels predicted infections in this study. However, the median time on OCR was a little over 2 years which may be too soon to see a difference in the rate of infection and immunoglobulin levels.